New targeted therapy for hemophilia

Maintenance of hemostasis is central to the prevention of thrombosis and bleeding. Diminished thrombin generation and clot formation arising from clotting factor deficiencies, such as hemophilia, disrupt this delicate balance and promote bleeding. Factor replacement is the standard of care for people with hemophilia in wealthy countries, but alternative hemostatic products are required if inhibitors to replacement factors develop. Although the factor VIII (FVIII) mimetic bispecific antibody emicizumab has enhanced the treatment of patients with hemophilia A with inhibitors, the need for alternative therapies for individuals with hemophilia B and other rare bleeding disorders has stimulated the generation of a plethora of new prohemostatic agents that target different facets of the coagulation system. Of these, novel therapies that can safely attenuate endogenous anticoagulant pathways may represent a solution to “rebalance” hemostasis in individuals with inherited or acquired bleeding disorders. To this end, antibody-mediated inhibition of tissue factor pathway inhibitor or aptamer-mediated suppression of antithrombin has already demonstrated positive outcomes in clinical trials with patients with hemophilia.